History of Research
Kozo Nakamura
The fi rst report of ossifi cation of the posterior lon- gitudinal ligament (OPLL) is credited to Key [1], who described it during the mid-nineteenth century.
Oppenheimer [2] later reported 18 cases with calcifi ca- tion or ossifi cation of the anterior and posterior liga- ments. In 1960, Tsukimoto [3] found OPLL during an autopsy. Following publication of this article, many Japanese surgeons reexamined their patients’ radio- graphs, which resulted in the discovery of numerous missed OPLLs.
In 1975, the Japanese Ministry of Public Health and Welfare (the present Ministry of Health, Labor, and Welfare) added OPLL as one of the specifi ed diseases for clarifi cation of etiology, epidemiology, and patho- genesis as well as establishment of criteria for diagnosis and treatment regimens. The Investigation Committee on Ossifi cation of the Posterior Longitudinal Ligament has taken the lead in the clinical and basic research of OPLL in Japan. The fi rst chairman, Tsuyama, conducted epidemiological, radiographic, pathological, and clini- cal studies. He was followed by the second chairman, Terayama, in 1981. A nationwide family study [4] of 347 cases was performed. Kurokawa took the third chair- manship in 1988, and he organized the studies into four subgroups: (1) genetic research; (2) study of the hyper- trophy and progression of OPLL; (3) the pathogenesis of myelopathy caused by OPLL; and (4) diagnostic cri- teria. Sakou took over in 1992, and biomolecular and genetic research [5] have been energetically conducted ever since. Harata, who became the fi fth chairman in 1996, conducted an epidemiological study [6] in China and assessed the quality of life in patients with OPLL [7]. In 2002, Nakamura became the sixth chairman and developed guidelines regarding OPLL for physicians [8].
Morbidity associated with OPLL in Japan is estimated to be 1.9%–3.2%. In other Asian and Eastern countries, the morbidity is equivalent or lower: 3.0% in Taiwan, 1.6%–1.8% in China, and 0.95% in Korea. In the Western world, it is 0.12% in the United States and 0.1% in
Germany [9]. Several members have investigated the relation between OPLL and calcium metabolism [10], diabetes, estrogen, and vitamin D. Diabetic patients were found to have a tendency to develop OPLL, and an abnormal secretion pattern of insulin by blood glucose was implicated [11]. Two animal models, the Zucker fatty rat [12] and the ttw (tip toe walking) mouse [13], were found to have ossifi cation of spinal ligaments, and their study has contributed signifi cantly to our under- standing of OPLL. The ossifi cation and compressed neural elements from surgical specimens or cadavers have been studied histologically [14]. Ossifi cation of the spinal ligament is ectopic, with hypertrophy of the ligament and proliferation of cartilaginous cells in the ligament and cytokines related to bone formation (bone morphogenetic protein and transforming growth factor-β) appearing during the ossifying process. In recent years, genetic analysis has been intensively per- formed in humans and animal models. Various candi- date genes were reported; three genes—COL11A2 [5], NPPS [13], and TGFb1—are most promising.
OPLL sometimes appears as long and multiple lesions and sometimes as ossifi cation of the dura. Patients with severe myelopathy and thoracic OPLL are most vulner- able to neurological deterioration. The treatment of thoracic OPLL is still controversial. Surgical treatment of OPLL always demands perfect planning and master- ful surgical skills.
Recording somatosensory evoked potentials (SEPs) was the fi rst modern monitoring method to detect spinal nerve dysfunction during surgical maneuvers.
Recently, multimodal spinal cord monitoring by SEPs and motor-evoked potentials (MEPs) [15] was proposed to fi nd any subtle abnormality in the spinal cord.
As for OPLL in the cervical spine, several new surgi- cal procedures have been developed after experiences with postlaminectomy kyphosis and subsequent neuro- logical deterioration. Kirita and colleagues developed a new laminectomy procedure that was substantially a new fusion technique, from which laminoplasty by Hattori evolved. Most popular is the open-door (unilat- eral) laminoplasty by Hirabayashi [16] and French- door (bilateral) laminoplasty of Kurokawa [17]. For the anterior approach, wide adhesion of OPLL to the dura Department of Orthopaedic Surgery, Faculty of Medicine,
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
3
4 K. Nakamura
or ossifi cation of the dura demands that the spinal surgeon do meticulous, skillful decompression.
Yamaura proposed the anterior fl oating technique, in which the ossifi cation is trimmed by a burr, promoting a shift ventrally [18].
The Investigation Committee on Ossifi cation of the Posterior Longitudinal Ligament functions as the hub of the basic and clinical research, which has made sig- nifi cant contribution to our understanding of this disease and to the development of spinbal surgery.
References
1. Key CA (1838) Paraplegia depending on the ligament of the spine. Guys Hosp Rep 3:173–174
2. Oppenheimer A (1942) Calcifi cation and ossifi cation of vertebral ligaments (spondylitis ossifi cans ligamentosa):
roentgen study of pathogenesis and clinical signifi cance.
Radiology 38:160–173
3. Tsukimoto H (1960) A case report: autopsy of the syn- drome of compression of the spinal cord owing to ossifi - cation within the spinal canal of the cervical spine (in Japanese). Nihon Geka Hokan (Arch Jpn Chir) 29:
1003–1007
4. Terayama K, Ohtsuka K, Wada K, et al (1986) Cross- sectional study—family study of the ossifi cation of the posterior longitudinal ligament (in Japanese). In: Investi- gation committee’s 1986 report on the ossifi cation of the spinal ligaments of the Japanese Ministry of Public Health and Welfare, Tokyo, pp 19–21
5. Koga H, Sakou T, Taketomi E, Hayashi K, Numaawa T, Harata S, Yone K, Matsunaga S, Otterud B, Inoue I, Leppert M (1998) Genetic mapping of ossifi cation of the posterior longitudinal ligament of the spine. Am J Hum Genet 62:1460–1467
6. Ueyama K, Harata S, Okada M, et al (2001) The ossifi ca- tion of the posterior longitudinal ligament in the cervical spine in China (in Japanese). In: Investigation commit- tee’s 2001 report on the ossifi cation of the spinal ligaments of the Japanese Ministry of Public Health and Welfare, Tokyo, pp 157–160
7. Fujiwara K, Kawai S, Harata S, et al (2002) Problems in patients with the posterior longitudinal ligament (in Japa- nese). In: Investigation committee’s 2002 report on the ossifi cation of the spinal ligaments of the Japanese Minis- try of Public Health and Welfare, Tokyo, pp 169–187
8. Yonenobu K (2004) Research on development of the ossi- fi cation of the posterior longitudinal ligament in the cervi- cal spine (in Japanese). In: Investigation committee’s 2004 report on the ossifi cation of the spinal ligaments of the Japanese Ministry of Public Health and Welfare, Tokyo, pp 87–88, 147–315
9. Sakou T, Matsunaga S (1996) Historical review: ossifi ca- tion of the posterior longitudinal ligament (in Japanese).
Nihon Sekitsui-geka Gakkai-shi 7:437–448
10. Seichi A, Hoshino Y, Ohnishi I, Kurokawa T (1992) The role of calcium metabolism abnormalities in the develop- ment of ossifi cation of the posterior longitudinal ligament of the cervical spine. Spine 17(S3):S30–S32
11. Akune T, Ogata N, Seichi A, Ohnishi I, Nakamura K, Kawaguchi H (2001) Insulin secretory response is posi- tively associated with the extent of ossifi cation of the pos- terior longitudinal ligament of the spine. J Bone Joint Surg Am 83:1537–1544
12. Okano T, Ishidou Y, Kato M, Imamura T, Yonemori K, Origuchi N, Matsunaga S, Yoshida H, ten Dijke P, Sakou T (1997) Orthotopic ossifi cation of the spinal ligaments of Zucker fatty rats: a possible animal model for ossifi cation of the human posterior longitudinal ligament. J Orthop Res 15:820–829
13. Okawa A, Ikegawa S, Nakamura I, Goto S, Moriya H, Nakamura Y (1998) Mapping of a gene responsible for twy (tip-toe walking Yoshimura), a mouse model of ossifi ca- tion of the posterior longitudinal ligament of the spine (OPLL). Mamm Genome 9(2):155–156
14. Ono K, Yonenobu K, Miyamoto S, Okada K (1999) Pathol- ogy of ossifi cation of the posterior longitudinal ligament and ligamentum fl avum. Clin Orthop 359:18–26
15. Matsuyama Y, Tsuji T, Yoshihara H, et al (2004) Surgical treatment of thoracic ossifi cation of posterior longitudi- nal ligament: intraoperative spinal cord monitoring (in Japanese). Bessatsu Seikei Geka 45:110–119
16. Ogawa Y, Toyama Y, Chiba K, Matsumoto M, Nakamura M, Takaishi H, Hirabayashi H, Hirabayashi K (2004) Long-term results of expansive open-door laminoplasty for ossifi cation of the posterior longitudinal ligament of the cervical spine. J Neurosurg Spine 1:168–174
17. Seichi A, Takeshita K, Ohishi I, Kawaguchi H, Akune T, Anamizu Y, Kitagawa T, Nakamura K (2001) Long-term results of double-door laminoplasty for cervical stenotic myelopathy. Spine 26:479–487
18. Matsuoka T, Yamaura I, Kurosa Y, Nakai O, Shindo S, Shinomiya K (2001) Long-term results of the anterior fl oating method for cervical myelopathy caused by ossifi - cation of the posterior longitudinal ligament. Spine 26:241–248
